This research is conducted jointly by Riverside Research Institute (RRI) and Weill Medical College of Cornell University (W1MC). Its long-term objective is to advance the diagnosis, treatment planning, and treatment monitoring of ocular diseases, primarily glaucoma, by interwoven engineering, and clinical studies. The program uses advanced methods to analyze radio-frequency (RF) echo signals and extract tissue information not available with conventional ultrasound systems. To examine anterior sections of the eye, novel very-high-frequency ultrasound (VHFU) annular arrays will be used with synthetic aperture and frequency-domain apodization; these will substantially improve resolution and depth-of-focus. Digital RF data will be acquired during multi-plane VHFU scanning of the entire anterior segment to construct highly detailed 3-D representations of structures involved in glaucoma and hypotony. Elements as small as 20-gm will be resolved. Biometric data (dimensions, surface areas, volumes) will be derived for relevant ocular compartments, including the anterior chamber and ciliary processes. Microstructure will be evaluated in terms of the effective sizes, concentrations, mechanical properties, and morphologic shapes of tissue constituents. Sizes of cell-level structures (15 gm) will be estimated to within 1 p.m to monitor changes related to function and therapy. These assays will use advanced 1-D and 2-D spectral techniques designed using a theoretical scattering model of tissue microstructure. The methods will be validated in laboratory and animal experiments. Measured features will be compared with light microscopy to elucidate sensitivity to specific microstructural elements. Animal and clinical studies will assess the utility of these methods for evaluating glaucoma, hypotony, and small anterior tumors undergoing treatment. Glaucoma studies will document ciliary body microanatomy and drug responses. Related studies will employ new high frequency transducers (20-30 MHz) and new morphological analysis techniques to examine posterior ocular structures. They will extract detailed tissue information from regions inaccessible to other imaging modalities. The methods will be clinically evaluated in cases of age-related macular generation.